Tuesday, April 30, 2013

Have you ever been asked by a medical professional to rate your pain level on a scale of zero to ten? Needless to say, this ranking system is highly subjective.

Even more problematically, it can’t be used for people who can’t speak (the very young or the cognitively impaired) nor can it be used to compare pain levels in different people. And yet, treatment for pain usually depends on understanding the intensity of that pain. Thanks to some new fMRI studies conducted by researchers led by Tor Wager from the University of Colorado, we may now have a neurological signal for physical pain.

You know a pain study isn't going to be good news for the volunteers. Wager and his colleagues do not disappoint. 114 participants were hooked up to an fMRI machine while heat was applied to their left forearms. The heat levels were calibrated for each individual to range from warm to scorching (subjective pain level 'seven'). Each test was preceded by a warning cue, 8 seconds of anticipation, 10 seconds of applied heat, and then a 4 second evaluation period. Some people went through 75 of these trials. There were some interesting variations. In one study, all the subjects had recently experienced a romantic rejection. These people got to look at either a picture of their ex-partner or of a close friend while being seared. In another, people were unwittingly given analgesics before the trials.

So, what did the scientists learn from all this? The fMRI scans indicated a ‘signature response’ to pain that became clearer as pain levels increased. Not only that, but the same pattern appeared in different people, indicating that it could be a universal signal of pain at the neurological level. People suffering from emotional pain, as with the heartbroken subjects viewing pictures of their exes, did not have the pain response pattern. People being treated with analgesics showed a dampened signature response.

All of this strongly suggests that doctors should be able to use fMRI scans to assess patient pain levels. Until that happens, here's another scale you might find useful:Wager, T., Atlas, L., Lindquist, M., Roy, M., Woo, C., & Kross, E. (2013). An fMRI-Based Neurologic Signature of Physical Pain New England Journal of Medicine, 368 (15), 1388-1397 DOI: 10.1056/NEJMoa1204471.

Monday, April 29, 2013

You already know that soft drinks are bad for you. But a single daily indulgence can’t be that bad can it? Sorry. According to a new study by the scientists in the InterAct Consortium at the Imperial College London, one sugar-sweetened soft drink per day can increase your risk of getting type 2 diabetes by 22%.

From 1991 to 2007, the InterAct project collected data on hundreds of thousands of people from eight European countries. None of the participants had type 2 diabetes when first recruited. By the end, over 12,000 of them did. These people were compared with 16,000 randomly selected non-diabetics.

The researchers asked the subjects about their consumption of sweet beverages, which were divided into juices and nectars (fruits or vegetables plus up to 20% added sugar) and soft drinks (sugar-sweetened or artificially sweetened). Participants were asked how often they consumed these sweet drinks, from less than one serving per month to at least one per day. A serving size was twelve fluid ounces, or 336 ml. Among other factors, the researchers adjusted for total calorie intake, body mass index (BMI), gender, educational level, physical activity and use of alcohol and/or tobacco.

The bad news is that drinking at least one sugar-sweetened soft drink per day increased a person’s risk of developing type 2 diabetes by 29%, compared with consuming fewer than one such beverage per month. The worse news is that the diabetes risk jumped by 22% when going from one to six drinks per week to one or more drinks per day. Because these categories were so broad, this could mean increasing from one drink per week to one per day, or from six per week to several per day. Either way, your safest bet is to consume fewer than one sugary soft drink per week.

The good news is that after accounting for BMI, there was no such association with either artificially sweetened soft drinks or with juices and nectars. So, if you really can’t palate plain water, you do have some options, at least as far as type 2 diabetes is concerned. I’ve written before about another peril of sugary drinks.

Here’s one more interesting thing. From 1992 to 2000, Europeans got about 2.5% of their daily carbohydrates from sugary drinks. For people in the U.S., that figure was over 10%. I’m amazed, and not in a good way.

Friday, April 26, 2013

Thanks to the media sensation of 2012, we’ve all heard of
the Maya Long Count (MLC) calendar. Needless to say, that calendar did not augur the
end of the world any more than our calendars do every December 31st. The
more interesting question is how well we can correlate events noted on the Maya
calendar with dates on our own calendar. Thanks to work led by Douglas Kennett
of Pennsylvania State University, we can now be pretty sure we have correctly matched up the two counting methods.

Let’s begin by explaining the MLC calendar. Just
as we divide our time periods into sections (millennia, years, days, etc), so
too did the Maya. Only, their system included five time units: Bak'tun (144,000
days), K'atun (7,200 days), Tun (360 days), Winal (20 days), and K'in (1 day).
In our system, we might designate a date as 4/26/2013 (or 26/4/2013 for you
Europeans) to show that it’s the twenty-sixth day of the fourth month in the
two thousand thirteenth year, or about 735,360 days (if I put in the right
number of leap years) since the starting point at 0/0/0. The Maya would have
designated that same time span as 5.2.2.12.0 (5 Bak’tuns, 2 K’atuns, 2 Tuns, 12
Winals and 0 K’ins). Of course they didn’t use our numeric system, so it would
have looked like a series of bars and dots.

Caption: Elaborately carved wooden lintel or ceiling from
a temple in the ancient Maya city of Tikal, Guatemala, that carries a carving
and dedication date in the Maya calendar.

Credit: Courtesy of the Museum der Kulturen.

Okay, so we know how to translate the MLC calendar to tell us how many days have passed since they began that count.
Unfortunately, that information alone doesn’t yield any insight into the
equivalent date on our calendar, because they didn’t start their calendar at
the same time as we started ours. Knowing that an event occurred 80,000 days into the MLC doesn’t tell you much if you don’t know when their day zero was.
You need to know what correction factor to add to the Maya count to bring it
into alignment with the European calendar.

There are two ways to find that correction factor. One is to
find an event that was recorded in both calendars. The most commonly used
correction, known as the Goodman-Martinez-Thompson (GMT) correlation, is
largely based on this sort of historical evidence. The second method is to
physically date artifacts that are from a specific Maya date. Kennett and his
colleagues followed this tactic.

The researchers took four samples from a wooden lintel in an
ancient Maya temple (shown above) that included a date commemorating the defeat of one
Maya king by his rival. The researchers used radiocarbon dating of the wooden lintel in conjunction with growth rate estimates for the tree from whence it had come to calculate the actual age of the lintel. From that, they figured out when the regicide had occurred.Among the various correlations, the GMT, placing the event depicted on the lintel during our year C.E. 695, proved to be most accurate. Other methods
of correlating Maya and European dates varied by as much as a five hundred years
either way. With this new information, we can now accurately match events that occurred on the MLC to dates that we can understand. Luckily, we all lived through 2012 to
appreciate this.

Thursday, April 25, 2013

Language is the hallmark characteristic that sets humans
apart from other animals. More than tool use, empathy or morality, all of which
are practiced by at least some non-humans, language makes us who we are. At
some point, we evolved the ability to turn a few dozen sounds into a limitless
number of expressions. Charles Yang of the University of Pennsylvania tried to
figure out when that happened by comparing two linguistically similar
creatures: very young children and chimpanzees. You won’t be surprised to learn
that they aren’t that similar after all.

The big question in language acquisition is how young
children get from speaking no words to complex sentences so quickly and
accurately. There are two prevailing ideas. One is that toddlers begin their
journey into language use with imitation. That is, they simply repeat the short
phrases that they hear adults say. Only after mastering those sentences do they
go on to improvise their own longer sentences. The second idea is that children
combine language elements independently from the very beginning, based on the
grammar of the speakers around them.

To evaluate these two possibilities, Yang noted how often
young language learners, speaking only two-word sentences, used ‘a’ or ‘the’
before nouns. He compared this ratio to that found in the Brown Corpus (a
collection of English language texts) and with over a million utterances
appearing in the public domain that were directed at children. In adult speech,
certain words tend to be paired almost exclusively with one or the other of
these determiners (we almost always refer to ‘the kitchen’ rather than ‘a
kitchen’), but young children used the two articles much more equally. This
strongly suggests that even at the very earliest stages of language
acquisition, they are not simply parroting back phrases they’ve previously
heard.

Obviously, chimpanzees don’t speak, but a few of them can
sign. Do they also combine signs independently of ones they’ve seen? Here, Yang
uses a sample size of one: the American Sign Language-using chimp named Nim
Chimpsky (after noted linguist Noam Chomsky). Unlike the human kids, Nim’s
language skills seemed to be based purely on memorization. He could not
improvise new combinations of signs.

This
corroborates that there really is something unique about human language. At
some point after we diverged from chimpanzees, we evolved the ability to
communicate in a fundamentally different way. How that happened is still a
mystery, and may remain so, since we can look to neither the fossil record nor
our living cousins for answers.

Yang, C. (2013). Ontogeny and phylogeny of language Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1216803110.

Wednesday, April 24, 2013

Wish you knew more about medicine or the human body but only have a minute to spare? Have I got the YouTube channel for you. With 'One Minute Medical School', Dr. Rob Tarzwell, a Clinical Assistant Professor at the University of British Columbia, has created a series of videos that address everything from radiation to wrist bones in one minute increments.Here's a sample, about chicken pox and shingles:By the way, Tarzwell's topics are often prompted by viewer request, so feel free to contact him on Facebook, Twitter or his website.Hat tip: Skeptically Speaking.

Tuesday, April 23, 2013

No matter where in the world the next epidemic starts, it’s
no more than a day’s plane ride from reaching anyone on the planet. Needless to
say, doctors are keen to stop diseases from spreading around the globe. To that
end, Kamran Khan of St. Michael’s Hospital, Toronto, and his colleagues have a
proposal: screen airline passengers as they depart from risky areas.

Screening airline passengers for infectious diseases may be a tempting idea in principle. In practice, it’s more complicated. Leaving
aside the issues of privacy and expense, it could add to already tedious
boarding procedures and lead to huge disruptions in travel. However, if we do
choose to implement screening practices, there are better and worse ways to do
it.

The most inefficient health screening checks are done at the
point of entry. Most passengers arriving at an airport were never exposed to
any dangerous diseases. Even people arriving from an at-risk location might not
have been there long enough to contract anything. For example, take air
travelers leaving Mexico during the 2009 H1N1 influenza pandemic. The researchers
estimated that catching any possible influenza carriers arriving from Mexico would
have required screening stations at 82 international airports spread through 26
countries. 116 people would have been screened at those entry points for every
person with any possibility of being infected. And that’s just counting direct
flights. Adding in all passengers traveling through Mexico on connecting
flights would have meant screening 67 million people in over a thousand
airports. Clearly, entry screening is not the way to go.

How about screening people as they leave a hazardous region? Again,
referring to the H1N1 pandemic, the researchers concluded that exit screening
at just eight Mexican airports would have caught 90% of the people who could have
been carrying the disease. Clearly, if you can choose where to conduct
your health screenings, exit points are the way to go.

There are a couple of problems with this strategy. The most
glaring one is that the scientists don’t say how air passengers should be
screened. How do you process that many people in a way that doesn’t unduly slow
down air traffic without missing anything? Also, screening only at exit points means
that other countries have to trust each other’s screening procedures. Plus,
there’s always the risk that a person will not begin to show symptoms until
after departing from the exit airport. Finally, these check points will most
likely only be used if there is some indication that an epidemic may be
brewing. By that time, at least a few contagious passengers will undoubtedly
have already been transported to new regions.

Friday, April 19, 2013

It’s been known for nearly a century that vaccines are more
effective when they include adjuvants. In fact, vaccines that don’t contain
entire live pathogens (which is most of them these days) work rather poorly
without adjuvants. Luckily, alum is a very good and safe adjuvant that can be
added to just about any vaccine. Unluckily, we didn’t used to have any idea of
how adjuvants work. That has now changed, thanks to work by researchers from
the University of Colorado and from the Howard Hughes Medical Institute.

To understand adjuvants, you have to understand vaccines at
the molecular level. What exactly is going on after the needle punctures your
arm? The immune system is immensely complex with myriad cellular and protein
actors that I can't possibly untangle here. Suffice it to say that one of the
first events is the arrival at the scene of a type of white blood cell called
the neutrophil. These first responders release
various chemical cues to encourage other cells to enter the fray. Among them
are the dendritic cells that engulf the antigens within the vaccine and display
them on their surfaces to T-cells. These T-cells in turn initiate antibody
production.

Where does the adjuvant come into the picture? Neutrophils
happen to be extremely short-lived cells. Very soon after encountering the
intruding antigens, the neutrophils die, releasing streams of DNA. If a vaccine
includes the adjuvant alum, that DNA will coat the alum. Then other dendritic
cells end up engulfing the entire complex of host DNA-alum-antigen. It turns out that
the T-cells are much more interested in the DNA-associated antigens; they form
longer and stronger interactions with dendritic cells that have ingested the
DNA-alum morass along with the target antigens. The scientists confirmed this
by adding DNase (an enzyme that digests DNA) along with their vaccines.

Amy McKee of the University of Colorado, and lead author of
the paper, explains:

The
DNA makes the antigen-presenting cell stickier. We believe that extended
engagement provides a stronger signal to the T-cell, which makes the immune
response more robust.

Why should this be so? We can't really answer that question yet. However, I find it intriguing that the adjuvant places host DNA in such close contact with the foreign antigen. Remember, it's the immune system's job to distinguish host from non-host. Perhaps this juxtaposition makes that contrast more stark.

Thursday, April 18, 2013

I’ve written before about the ‘marshmallow test’ for self-control. If you haven’t seen that post, I recommend checking it out as the results may surprise you. What may be even more surprising is that humans aren’t the only creatures who can delay gratification. Alice Auersperg and her colleagues from the University of Vienna have subjected Goffin cockatoos to a similar test and found that they too are capable of restraining themselves.
Delayed gratification tests usually involve the promise that if the participant can avoid eating the treat in front of them, they'll get something even better. They've been done on other kinds of birds, most notably corvids (crows and ravens). These birds have been known to wait for up to five minutes for a better offer. However, corvids have the habit of hoarding their food, which might make it easier for them to postpone eating their treats. Cockatoos have no such trait.
Fourteen cockatoos were given the chance to rank three possible treats (pecan, cashew or fried meat). After that, they were taught to exchange less desirable items for more desirable items as shown in the video below.

Notice that the experimenter keeps the more desirable tidbit visible but out of reach in her left hand. The cockatoo is only allowed to exchange for it when the person reopens her right hand after a predetermined delay (in this case, 40 seconds). All the birds could delay eating the first item for at least a couple of seconds. Remember, they held that morsel in their mouths, unlike the corvids who tended to temporarily discard it. I'm not sure how many of us could wait even that long with a marshmallow in our mouths. Half the birds could wait forty seconds and three waited nearly a minute and a half. When the choice was between one item now and either two or six of the same item later, fewer of the birds were interested in trading, but eight of them did hold out for twenty seconds. Interestingly, the birds tended to either wait the entire duration or give up immediately. The authors speculate that the cockatoos were able to judge the time duration and decide if the expected benefit was worth the wait. This is reminiscent of the children judging the reliability of the experimenter in the post I mentioned earlier.

Wednesday, April 17, 2013

If you’re in law enforcement, how do you stop a speeding car
without risking injury to yourself or to the occupants of that or any other
car? The folks at Engineering Science Analysis Corporation used funding from
Homeland Security's Science & Technology Directorate to develop the Safe,
Quick, Undercarriage Immobilization Device
(SQUID) program, which includes the following two technologies:

The Pit-Ballistic Undercarriage Lanyard (Pit-BUL™):

In case it wasn’t clear in the video, the net contains
spikes that puncture the tire. That car is going nowhere.

The NightHawk™:

Again,
the strip contains spikes. Either of these devices can be triggered remotely or
activated by motion sensors.

Tuesday, April 16, 2013

The more we learn about the brain, the less control we seem
to have over our own thoughts and actions. We feel fully
conscious and in command of the decisions we make. We also feel as if all our
thoughts are coming from a single entity in a united all-controlling mind. None
of that is true. Need some evidence? Chun Siong Soon and his colleagues
designed an experiment to illustrate the order of events between the conscious decision to do something and the
action itself. Spoiler alert: the action comes first.

The researchers used some rather nuanced experiments to suss
out the timing between decision and action. Briefly, numbers were flashed on a
screen in front of 18 volunteers while fMRI machines recorded their brain
activity. At some point, and at their own volition, the participants decided to
either add or subtract the next two numbers shown. They recorded both the
moment of that decision and the answer they got. You can read a more complete
explanation at Why Evolution is True.

What were the results?

Four seconds before the person stopped the clock with
the thought, ‘I’ve now decided that I will be adding the next two numbers I
see’, his brain activity indicated that he would be performing that action. In
other words, the researchers could see the forthcoming action take shape in the
subject’s brain well before he himself was aware of having decided anything.
Not only that, but researchers were able to predict with 59% accuracy whether
the forthcoming math operation would be addition or subtraction. Remember, the
scientists were basing this prediction on brain activity occurring some time
before the person himself knew when or what the next mathematical operation would
be.
This phenomenon has been dubbed the 'Bereitschaftspotential' (German for 'readiness
potential'), or BP, and it suggests that we can at best veto an action the unconscious parts of our brains have already decided to take. Similar experiments have shown that
the BP can occur up to ten seconds before the conscious part of our brains gets
clued in. Needless to say, this is completely counterintuitive and could
mean that many of our ‘decisions’ are actually rationalizations after the fact.
For whatever reason, part of our brains wants to perform an action and it
convinces the aware part of us that that’s what we had planned all along.
To be clear, none of this changes the fact that we really
feel as if we are the masters of our own behavior, nor does it alter our responsibility for our conduct. Our actions have consequences for us and others regardless of what part of our brains instigated them.

Monday, April 15, 2013

Blood typing (determining what kinds of antigens a person
has on the surface of his or her red blood cells) is a series business. Giving
a person the wrong type of blood can have dire consequences. Unfortunately,
blood typing is also complicated by the fact that there are so many different
classes of antigens to consider (for more background, see my post on the discovery of two new blood groups). Just when you think you’ve covered all your bases, someone succumbs to
an acute hemolytic transfusion reaction because of a previously unidentified
red blood cell antigen.

One such unhappy event happened in 1952 when a patient
referred to as ‘Mrs. Vel’ nearly died after receiving what her doctors thought
was a perfectly compatible blood transfusion. It turns out that Mrs. Vel was
missing an antigen (later called the Vel antigen) present in the donated blood.
This discrepancy resulted in the widespread destruction of her red blood cells.

In an effort to avoid repeating this error, researchers
screened tens of thousands of donated blood samples to see which, if any, would
not cross react with Mrs. Vel’s blood. The scientists found that only about one
person in two thousand was missing the Vel antigen. This effectively means
that people like Mrs. Vel are probably out of luck if they need a blood
transfusion. More importantly, it means that it’s critical to identify Vel
minus people before giving them blood of any kind.

Needless to say, finding the Vel gene would make the
screening process much easier. Now, many of the same researchers who brought you the Langereis and Junior blood groups have done just that. The scientists
discovered that a gene known as SMIM1
was responsible for encoding the Vel antigen. Vel minus people are missing
seventeen nucleotides from their copies of this gene, effectively nullifying
the protein as a surface antigen.

This should make it much easier to rapidly identify Vel
minus people before they receive life-threatening blood transfusions. It also
brings the number of blood typing groups up to 33. Luckily, blood typing tends
to be automated these days, so most people have no need to remember all 33
factors. Personally, I only know my blood type for two blood systems: ABO and
rhesus. Statistically speaking, I’m probably Vel plus, and I have no idea for
the other thirty groups.

Friday, April 12, 2013

Stanford researchers, led by Kwanghun Chung, have developed
an amazing tool for seeing the inner workings of the brain. In an obvious
attempt to fit their chosen acronym of CLARITY (and an excellent acronym it
is), they named their technique Clear Lipid-exchanged Anatomically Rigid
Imaging/immunostaining-compatible Tissue hYdrogel. Nicely
done.

CLARITY transformation of a mouse
brain at left into a transparent but still intact brain at right. Shown
superimposed over a quote from the great Spanish neuroanatomist Ramon y Cajal.

So, how do you make a brain transparent? Here’s the extremely
simplified recipe:

Step one: Infuse your brain with a mix of chemicals
(acrylamide, bisacrylamide and formaldehyde) that bind to proteins, nucleic
acids and small molecules, but critically, not to lipids (fats)

Step two: Allow the chemicals to solidify into a gel that
permeates the entire brain. The molecules listed in step one are locked in place by this acrylamide matrix.

Step three: Run an electric current through the brain to
eliminate everything not attached to the acrylamide gel (i.e. the
light-reflecting lipids). The result is a totally transparent brain, as shown above.

Step
four: Add your stain or stains of choice.

Three-dimensional
view of stained hippocampus showing:

fluorescent-expressing
neurons (green)

connecting
interneurons (red)

supporting
glia (blue).

Credit:
Courtesy of the Deisseroth lab.

What can be done with this technique? A better question might be 'what can't you do with it?' Not only could you directly
compare the brain structures of people with and without diseases like
Alzheimer’s, cancer or autism, but you could see how different parts of the brain interact with each other. Unlike with current brain staining technologies, you can look at entire brains rather than only at thin slices of brain tissue.

Thursday, April 11, 2013

Gastric bypass surgery is a highly effective treatment for
obesity. It involves surgically sealing off or
removing most of a person’s stomach and attaching the remaining small stomach
pocket to the small intestine. Thus, a person is only able to eat a small
amount before feeling full. You may think that this inability to eat large
meals is the driving force behind the high success rate of gastric bypass.
While that is important, it may not be the main factor. It may be more about
the microbes.

Alice Liou of Massachusetts General Hospital and her
colleagues used a mouse model of gastric bypass to compare the pre-and
post-operative fauna in the digestive tracts of mice with diet-induced obesity.
One group (GB) received gastric bypass surgery similar to that used in humans.
The second (SHAM) also underwent surgery but that operation did not result in gastric
bypass. All the mice were fed a liquid diet for two weeks and then were
allowed to eat as much as they liked.

Post surgery, the GB mice maintained normal
weights while the SHAM mice quickly regained their obese statures. So, far this is no surprise. After all the SHAM mice had not had gastric bypass. However, there were significant differences in the composition of the gut microbes
between GB mice and the SHAM mice. In other words, having real gastric bypass surgery affected the make-up
of the mice’s intestinal flora. This was true regardless of whether the mice
were fed a normal or a high fat diet.

Here’s the fascinating part: the scientists inoculated
germ-free mice (mice with no gut bacteria of their own) with fecal samples from the GB or SHAM mice. In effect, the researchers were transplanting the intestinal environment of the GB or SHAM mice into the germ-line mice without surgery. The germ-free mice that received gut bacteria from the GB mice
lost weight and fat tissue. This was without any diet restrictions. In contrast, mice receiving fecal matter from SHAM mice did not lose weight. This strongly suggests that it is the altered microbial environment of the gut rather than meal size restriction that drives gastric bypass weight loss.

This is actually a hopeful sign. It means that we might be
able to achieve the same results as gastric bypass surgery by simply
manipulating a person’s microbial content. The bad news is that we’re far from
understanding how to do this safely. We don't know what it is about gastric bypass that causes the change in bacterial population and we don't know exactly which of those changes are critical for weight loss. Still, it's a start.

Stochastic Scientist? What's up with that?

Why the Stochastic Scientist? As I'm sure you all know, 'stochastic' is another word for 'random', which is what I intend for the focus of this blog. Although my formal training is as a molecular biologist, there are many other fields of science that are also fascinating and beautiful. It's my intention to blog about which ever scientific discovery or invention catches my, and hopefully your, fancy.

I also hope to inspire people to learn more about science. By choosing among a huge variety of scientific endeavors, I'll undoubtably hit upon something that will pique my readers' interest.

I guess I could have called my blog 'The Joy of Science', but that wouldn't have been quite so random.